Studies of the relation between long-chain fatty acid oxidation and gluconeogenesis are being pursued in isolated hepatocytes from fasted rats. Our preliminary data suggest that long-chain fatty acids may augment gluconeogenesis, even when their oxidation is blocked by octanoyl - D (plus) carnitine. Therefore it is conceivable that the intact fatty acid molecule, itself - or its CoA ester - stimulated gluconeogenesis. In future experiments we expect to study the effects of octanoic acid on gluconeogenesis - earlier work did not show a major effect of octanoate on gluconeogenesis in liver - and to determine whether octanoic acid alters the gluconeogenic response to palmitic acid. We will also reexamine the relationship between intrahepatic acetyl CoA levels and gluconeogenesis, manipulating these levels with agents like lipoic acid and acetylcarnitine. Other experiments are concerned with certain aspects of carbohydrate and lipid metabolism in human platelets and their possible relation to hemostatic function of platelets: 1) effects of insulin, diabetes, and diet on glycolysis and lipid syntesis; 2) the possibility that platelets possess phosphoenolpyruvate carboxykinase, pyruvate carboxylase, and malic enzyme and the alterations in enzyme activities caused by diabetes or exposure to insulin; 3) the effect of insulin and diabetes on flux through the Embden-Meyerhof and hexose monophosphate shunt pathways; 4) the effect of insulin, diabetes, and diet on platelet aggregation.